Photophysical and electrochemical properties of protriptyline hydrochloride (PTL-HCl) and its free base were measured in different solvents. Ground-state properties remain unchanged as a function of solvent or protonation state. The fluorescence quantum yield and lifetime, on the other hand, are solvent-dependent. Fluorescence lifetimes results were obtained from monoexponential decay fittings. Characterization of the 266 run nanosecond laser flash photolysis species reveals the presence of the triplet-triplet transient intermediate at low-intensity conditions. At high laser intensities, two new transient intermediates were observed, which were assigned to the solvated electron and the radical cation. These species are formed through a biphotonic route, as shown with photonicity studies. The relatively high oxidation potentials measured for PTL-HCl and its free base corroborate the biphotonic process required for these species. These electrochemical studies also show that PTL-HCl is easier to oxidize than its free base. Singlet oxygen is established as one of the transient species following triplet-state formation. The PTL-HCl triplet state is probably involved in the dimer formation and other reactive intermediates, and therefore, it might be directly associated with the in vivo phototoxic effects observed for this drug.